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超重和肥胖乳腺癌女性术前减肥试验中,粪便阿克曼氏菌黏蛋白相关菌与体成分和微生物多样性相关。

Fecal Akkermansia muciniphila Is Associated with Body Composition and Microbiota Diversity in Overweight and Obese Women with Breast Cancer Participating in a Presurgical Weight Loss Trial.

出版信息

J Acad Nutr Diet. 2020 Apr;120(4):650-659. doi: 10.1016/j.jand.2018.08.164. Epub 2018 Nov 9.

Abstract

BACKGROUND

Akkermansia muciniphila (AM) is a gram-negative, mucin-degrading bacteria inhabiting the gastrointestinal tract associated with host phenotypes and disease states.

OBJECTIVE

Explore characteristics of overweight and obese female early-stage (0 to II) breast cancer patients with low AM relative abundance (LAM) vs high (HAM) enrolled in a presurgical weight-loss trial.

DESIGN

Secondary analysis of pooled participants in a randomized controlled trial (NCT02224807).

PARTICIPANTS/SETTING: During the period from 2014 to 2017, 32 female patients with breast cancer were randomized to weight-loss or attention-control arms from time of diagnosis-to-lumpectomy (mean=30±9 days).

INTERVENTION

All were instructed to correct nutrient deficiencies via food sources and on upper-body exercises. The weight-loss group received additional guidance to promote 0.5 to 1 kg/wk weight-loss via energy restriction and aerobic exercise.

MAIN OUTCOME MEASURES

At baseline and follow-up, sera, fecal samples, two-24 hour dietary recalls and dual x-ray absorptiometry were obtained. Bacterial DNA was isolated from feces and polymerase chain reaction (16S) amplified. Inflammatory cytokines were measured in sera.

STATISTICAL ANALYSES PERFORMED

Differences between LAM and HAM participants were analyzed using t tests and nonparametric tests. Spearman correlations explored relationships between continuous variables.

RESULTS

Participants were aged 61±9 years with body mass index 34.8±6. Mean AM relative abundance was 0.02% (0.007% to 0.06%) and 1.59% (0.59% to 13.57%) for LAM and HAM participants, respectively. At baseline, women with HAM vs LAM had lower fat mass (38.9±11.2 kg vs 46.4±9.0 kg; P=0.044). Alpha diversity (ie, species richness) was higher in women with HAM (360.8±84.8 vs 282.4±69.6; P=0.008) at baseline, but attenuated after weight-loss (P=0.058). At baseline, interleukin-6 level was associated with species richness (ρ=-0.471, P=0.008) and fat mass (ρ=0.529, P=0.002), but not AM. Change in total dietary fiber was positively associated with AM in LAM (ρ=0.626, P=0.002), but not HAM (ρ=0.436, P=0.180) participants.

CONCLUSIONS

Among women with early-stage breast cancer, body composition is associated with AM, microbiota diversity, and interleukin-6 level. AM may mediate the effects of dietary fiber in improving microbiota composition.

摘要

背景

阿克曼氏菌(Akkermansia muciniphila,AM)是一种革兰氏阴性、黏液降解细菌,栖息于胃肠道,与宿主表型和疾病状态有关。

目的

探索超重和肥胖的早期(0 期至 2 期)乳腺癌女性患者中相对丰度较低(LAM)与相对丰度较高(HAM)的 AM 与参与一项术前减肥试验的患者特征之间的关系。

设计

随机对照试验(NCT02224807)的二次分析。

参与者/设置:2014 年至 2017 年期间,32 名乳腺癌女性患者在诊断至乳房肿瘤切除术(平均=30±9 天)期间被随机分配至减肥或对照组。

干预措施

所有患者均通过食物来源和上半身运动纠正营养缺乏。减肥组接受额外的指导,通过能量限制和有氧运动来促进每周 0.5 至 1 公斤的减肥。

主要观察指标

在基线和随访时,采集血清、粪便样本、两次 24 小时饮食回顾和双能 X 线吸收法。从粪便中提取细菌 DNA,并进行聚合酶链反应(16S)扩增。测量血清中的炎症细胞因子。

统计学分析

使用 t 检验和非参数检验分析 LAM 和 HAM 参与者之间的差异。Spearman 相关性分析用于探索连续变量之间的关系。

结果

参与者的年龄为 61±9 岁,体重指数为 34.8±6。AM 的相对丰度分别为 0.02%(0.007%至 0.06%)和 1.59%(0.59%至 13.57%),LAM 和 HAM 参与者分别为 0.02%(0.007%至 0.06%)和 1.59%(0.59%至 13.57%)。在基线时,与 HAM 组相比,HAM 组女性的脂肪量(38.9±11.2 kg 比 46.4±9.0 kg;P=0.044)更低。基线时,HAM 组女性的 alpha 多样性(即物种丰富度)更高(360.8±84.8 比 282.4±69.6;P=0.008),但减肥后有所减弱(P=0.058)。在基线时,白细胞介素-6 水平与物种丰富度(ρ=-0.471,P=0.008)和脂肪量(ρ=0.529,P=0.002)呈负相关,但与 AM 无关。总膳食纤维的变化与 LAM 中的 AM 呈正相关(ρ=0.626,P=0.002),但与 HAM 无相关性(ρ=0.436,P=0.180)。

结论

在早期乳腺癌女性中,体成分与 AM、微生物多样性和白细胞介素-6 水平有关。AM 可能介导膳食纤维对改善微生物组成的作用。

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